ES2748030T3 - Shielding device - Google Patents

Abstract

A system (1) comprising: (i) a capsule holder (2) having a lower end (2a) and an upper end (2b), wherein said capsule holder comprises a solid base (2c) located at said lower end ( 2a), a solid body (2d) extending upward from said solid base (2c) and a well (2e) extending downward into said solid body (2d), into which said well (2e) empties at the upper end (2b) of said capsule holder (2) and ends before said solid base (2c) and is configured to receive a lower half (3a) of a capsule (3), in which said capsule holder (2) is formed from a radiation shielding material, wherein preferably the radiation shielding material comprises lead, steel, or tungsten; (ii) a shielded needle positioner (4) having a lower end (4a) and an upper end (4b), wherein said shielded needle positioner (4) comprises a solid body (4c) defining a hole ( 4d) extending substantially linearly and centrally through it, said hole (4d) comprising a lower section (4e) leading to said lower end (4a), and an upper section (4f) leading to said end upper (4b) and configured to receive an upper half (3b) of a capsule (3), wherein said shielded needle positioner (4) is formed from a radiation shielding material, characterized in that said hole it is configured to fit over, and contain, the solid body of said capsule holder.

Description

DESCRIPTION

Shielding device

Technical field of the invention

The present invention relates to the field of radioactive substances and, in particular, to the handling of radioactive solutions. The present invention provides a device that enables the preparation of radioactive filled capsules. More particularly, the radioactive filled capsules are suitable for oral administration, which is used in certain radiopharmaceutical procedures.

Description of the related art

Radiopharmaceuticals are administered to patients orally or by intravenous injection. One method for oral administration is through a small capsule containing a diagnostic or therapeutic dose of the radioactive isotope. These capsules are routinely prepared in nuclear pharmacies by manually injecting into the capsules a solution containing the radioactive isotope, typically made from hard gelatin. In a known process, a large gelatin capsule and a small gelatin capsule are used for each dose prepared. Each large capsule is two-part and empty, and each small capsule may contain an absorbent buffer solution, such as Anhydrous Dibasic Sodium Phosphate USP. The required volume of a radioactive solution to produce the required dose in MBq or mCi is calculated based on the calibration date and the radionuclide concentration. The large capsule is pulled apart and the small capsule is placed within the lower half of the large capsule. The volume of radioactive solution is withdrawn using a shielded syringe and is then injected into the upper center of the small capsule. The top of the large capsule is then secured around the lower half so that the small capsule is contained within the large capsule. Following measurement of the patient dose in a suitable radioactivity calibration system, said dose is administered to a patient.

This known capsule filling process is manual and therefore subject to variations between individual operators. This is problematic for the accuracy and uniformity of the patient doses inside the capsule. Furthermore, although shielding around the syringe is primarily used in this manual process, no shielding is provided around the capsule itself, thereby providing a high radiation load to the operator's hands. Furthermore, this manual process is prone to spills and needle stick injuries.

US7343724 describes a method and apparatus for accurate dispensing of radiopharmaceuticals from a sealed source vial into capsules.

Therefore, it would be desirable to have better accuracy and uniformity of patient doses, a reduced radiation load, and a reduced chance of a spill or needle stick injury.

Summary of the invention

The present invention provides a system (1) comprising:

(i) a capsule holder (2) having a lower end (2a) and an upper end (2b), wherein said capsule holder comprises a solid base (2c) located at said lower end (2a), a solid body (2d ) extending upwards from said solid base (2c) and a well (2e) extending downwards inside said solid body (2d), in which said well (2e) ends at the upper end (2b) of said capsule holder (2) and ends before said solid base (2c) and is configured to receive a lower half (3a) of a capsule (3), in which said capsule holder (2) is formed from a shielding material against radiation;

(ii) an armored needle positioner (4) having a lower end (4a) and an upper end (4b), wherein said armored needle positioner (4) comprises a solid body (4c) defining a hole ( 4d) that extends substantially linearly and centrally therethrough, said hole (4d) comprising a lower section (4e) that opens into said lower end (4a) and configured to fit over the solid body (2d) , and contain it, of said capsule holder (2), and an upper section (4f) that opens into said upper end (4b) and configured to receive an upper half (3b) of a capsule (3), in which said positioner of Shielded needles (4) is formed from a radiation shielding material.

The present invention also provides a method for filling a radioactivity capsule (3), wherein said capsule comprises an inner shell (3c) and an outer shell (3d), wherein said outer shell (3d) comprises a body of smaller diameter (3e) and a larger diameter cover (3f) and in which said method comprises the following steps:

(a) provide the system of the invention as defined herein;

(b) placing said smaller diameter body (3e) inside the well (2e) of the capsule holder (2);

(c) placing said inner cover (3c) inside said smaller diameter body (3e);

(d) place the armored needle positioner (4) on the capsule holder (2) containing the smallest diameter body (3e) and the inner cover (3c) so that the solid body (2d) of the capsule holder (2) is contained within the lower section (4e) of the hole (4d) of the armored needle positioner (4) and an upper half of the inner cover (3c) is contained within the upper section (4f) of the hole (4d) of the positioner armored needle (4);

(e) introducing a first needle (7a), attached to a shielded syringe (7) containing a radioactivity solution in the upper section (4f) of the hole (4d), in the upper end (4b) of said needle positioner armored (4);

(f) injecting the radioactivity solution into the inner cover (3c);

(g) remove the armored needle positioner (4);

(h) fixing said larger diameter cover (3f) to said smaller diameter body (3e) so that said inner cover (3c) is safely contained within said outer cover.

The present invention provides improved precision and uniformity of patient doses. In addition, the possibility of spills and needle stick injuries is reduced and the radiation load is reduced.

The invention makes filling oral capsules with a radioactive solution safe and easy. It offers radiation protection through a shield around the entire filling process. It also ensures the correct placement of the syringe and needle in each case, resulting in an accurate and uniform patient dose inside the capsule. Furthermore, the inventive system allows the operator to fill the capsules faster, which also reduces the radiation load for said operator.

The system and method of the invention are of relevance to all places where the oral capsules have to be filled with radioactive solution or other dangerous solution. In the USA USA There are over 400 nuclear pharmacies preparing such oral capsules, which could benefit from the use of the present invention.

Brief description of the figures

Figure 1 is a schematic diagram of a non-limiting example of a system (1) of the present invention. A capsule holder (2) is shown, with a capsule (3) inside, covered by an armored needle positioner (4). Also shown is a needle (7a) attached to a syringe (7), in which the needle (7a) is entering the capsule (3), as would be the case in which a radioactive solution was being injected into the capsule.

Figure 2 is a schematic diagram of a non-limiting example of a capsule (3), showing how the inner cover (3c) is contained within an outer cover (3d) formed from two pieces, that is, a body smaller diameter (3e) and a larger diameter cover (3f).

Figure 3 depicts a non-limiting example of various components of an exemplary system of the present invention. From left to right a capsule holder (2), a preliminary needle positioner (6) with a screw (6g) and an armored needle positioner (4) are shown.

Figure 4 represents the system of figure 3, seen from the top. The solid base (2c) and the well (2e) of the capsule holder (2) can be seen. The screw (6g) and the hole (6d) of the preliminary needle positioner (6) can be seen. You can see the hole (4d) of the armored needle positioner (4). Also in the illustrated embodiment of the armored needle positioner, it can be seen that it is formed from two independent parts, that is, a main body and a cover. This embodiment facilitates access to the interior hole, which is useful, e.g. eg for cleaning.

Figure 5 shows the same components as in Figure 4, but they are located flat on a surface.

Figure 6 is a view from the bottom side of the same components as Figure 4.

Figure 7 shows an exemplary configuration of a system of the present invention, depicting the capsule holder (2), the shielded needle positioner (4), and the preliminary needle positioner (6) in a hot cell in preparation for carrying out an embodiment of the method of the invention.

Figure 8 is a graph showing the uniformity of capsule activity obtained using an exemplary method of the present invention ("Capsule Fill Shielding") as compared to the prior art method.

Figure 9 shows radiation exposure to hands in the prior art method compared to an exemplary method of the invention ("CFS").

Detailed description of the preferred embodiments

The terms "comprising" or "comprising" have their usual meaning throughout this application and imply that the agent or composition must have the essential characteristics or components listed, but that others may also be present. The term "comprising" includes, as a preferred subset, "consisting essentially of", meaning that the composition has the listed components, with no other characteristics or components present.

The term "capsule", as used herein, is intended to refer to a pharmaceutical preparation comprising a hard or soft coating, typically containing a single dose of active substance. In one embodiment, said capsule is intended for oral administration. Such capsules are well known to those skilled in the art and are described in the American and European Pharmacopoeia. The capsule shell can be made of a biodegradable material, for example gelatin, starch or other similar substances, which allows the contents to be released after the attack of digestive fluids. The consistency of the coating material can be adjusted by the addition of substances such as glycerol or sorbitol. Excipients such as surfactants, opaque fillers, antimicrobial preservatives, sweeteners, coloring matter authorized by the competent authority and flavoring substances can be added. The capsules may bear superficial marks. Hard shell capsules for human use are in a size range from # 5, the smallest, to # 000, which is the largest. Size # 00 is generally the largest size acceptable to patients (see, eg, Chapter 6: "Pharmaceutical Calculations", 2016, Jones and Bartlett Learning; Payal Agarwal, Ed.). In certain embodiments, the capsules include content of a solid, liquid, or pasty-like consistency, comprising one or more active substances with or without excipients such as solvents, diluents, lubricants, disintegrating agents, reducing agents, pH adjusting agents, and stabilizers. Suitably, the contents should not damage the cover and, to prevent any leakage, the cover should be properly sealed. For absorption and retention of a quantity of a radioactive solution, the small capsule may contain a hydroscopic crystalline powder. 123I capsules are well known in the art (see, eg, Chapter 34: "lodine Chemistry and Applications", 2015, John Wiley &Sons; Tatsuo Kaiho, Ed.).

The term "solid" is used herein in connection with various components of the system of the invention and has its normal meaning, ie, firm and stable in shape.

The terms "top" and "bottom" are used herein in connection with various components of the system of the invention and describe such components when they are typically located within the system of the invention, for example as illustrated in embodiment no. limiting figure 1.

The expressions "extending upwards" and "extending downwards" have their normal meaning, that is, towards a higher place and towards a lower place, respectively.

The term "well" refers to a depression or a closed space that is designed to provide sufficient space to accommodate and orient a capsule within it.

The term "radiation shielding material" refers to any one of several high atomic number (Z) materials that absorb radiation and can be used as radiation protection. For alpha particles, where the interval is very short, a very thin layer of material is sufficient. For beta particles, the shield is ideally first a layer of a material with a low atomic number, eg. eg followed by a second layer of a material with a high atomic number. Gamma radiation, on the other hand, is highly penetrating and therefore a highly absorbent material should be used. For economic reasons, lead (Pb) is the most commonly used for this purpose. Another frequently used material is tungsten (W). Tungsten has the advantage of being a robust material, unlike lead, which is relatively soft. The reader is referred for more detail to Saha GB: "Physics and Radiobiology of Nuclear Medicine" (New York: Springer; 2001, p. 218).

In an embodiment of the system (1) of the invention, said armored needle positioner (4) further comprises a cover (4g) configured to fit on the upper end (4b) thereof, in which said cover comprises a hole (4h) ) through it having a width similar to the upper section (4f) of the hole (4d) of the armored needle positioner (4), in which said cover (4g) is formed from a shielding material against the radiation.

In an embodiment of the system (1) of the invention, said radiation shielding material comprises lead, steel or tungsten.

In one embodiment, the system (1) of the invention further comprises:

(Ni) a preliminary needle positioner (6) having a lower end (6a) and an upper end (6b), in which said preliminary needle positioner (6) comprises a body (6c) defining a hole (6d ) extending substantially linearly and centrally therethrough, said hole (6d) comprising a lower section (6e) which opens into said lower end (6a) and configured to fit over the solid body (2d), and contain it, of said capsule holder (2), and an upper section (6f) that opens into said upper end (6b) and configured to contain an upper half (3b) of a capsule (3), in which said needle positioner armored (6) is formed from a rigid material.

With this embodiment, it is possible to purge the inner capsule with a larger orifice needle first, and also to provide a target for injection of a radioactivity solution thereafter. The diameter of the needle is indicated by the gauge of the needle. Different needle lengths are available for any given gauge. There are several systems for calibrating needles, including the Stubs Needle Gauge and the French Catheter Scale. Smaller gauge numbers indicate larger outer diameters. Needles in common medical use range from 7 gauge (largest) to 33 gauge (smallest) on the Stubs scale. A list with a gauge comparison diagram can be found, eg. Eg at the following link: https://en.wikipedia.org/wiki/Needle_gauge_comparison_chart. An International Standard is available to establish a color code for the identification of single-use hypodermic needles of nominal outside diameters (ISO 7864: 1993 Sterile single-use hypodermic needles).

In an embodiment of the system (1) of the invention, each of the components is substantially cylindrical.

In an embodiment of the system (1) of the invention, said rigid material comprises a rigid plastic. A suitable plastic is one that is readily available and easily manufactured, eg. eg, by injection molding or machining, without having to use tools with difficulty. In one embodiment, said rigid material is transparent, but this is not essential.

In an embodiment of the system (1) of the invention, said rigid material comprises plexiglass.

In an embodiment of the system (1) of the invention, said rigid material comprises a metal.

In an embodiment of the system (1) of the invention, said body (6c) of said preliminary needle positioner (6) is solid.

In an embodiment of the system (1) of the invention, said body (6c) of said preliminary needle positioner (6) is a frame.

An embodiment of the system (1) of the invention further comprises securing means (6g) configured to support a needle inside the hole (6d) of said preliminary needle positioner (6).

In an embodiment of the system (1) of the invention, said securing means (6g) comprise a spring or a screw. Suitable examples of securing means will be apparent to those skilled in the art, eg. eg, stainless steel springs or screws. The function is to fix the syringe in place to puncture multiple capsules.

In one embodiment of the method of the invention, steps (a) - (h) are carried out sequentially.

In an embodiment of the method of the invention, said capsule (3) is suitable for oral administration.

In an embodiment of the method of the invention, said capsule (3) is made from a material comprising gelatin or polymer formulated from cellulose.

In an embodiment of the method of the invention, said capsule (3) is made from hard gelatin.

In an embodiment of the method of the invention, said inner cover (3c) contains an absorbent buffer solution.

In an embodiment of the method of the invention, said absorbent buffer solution comprises a hydroscopic crystalline powder.

In an embodiment of the method of the invention, said absorbent buffer solution is anhydrous dibasic sodium phosphate USP. In a particular embodiment, said absorbent buffer solution is about 200 to 500 mg of anhydrous dibasic sodium phosphate USP.

In an embodiment of the method of the invention, said inner cover (3c) contains a stabilizer.

In an embodiment of the method of the invention, said stabilizer is disodium edetate dihydrate.

In an embodiment of the method of the invention, said inner cover (3c) contains a reducing agent.

In an embodiment of the method of the invention, said reducing agent is sodium thiosulfate pentahydrate.

In an embodiment of the method of the invention, at the end of said method, the pH of the content of said inner shell (3c) is in the range of 7.5 to 9.0.

In one embodiment of the method of the invention, said radioactivity solution comprises a radioactive isotope suitable for use as an orally administered radiopharmaceutical.

The following list provides non-limiting examples of radiopharmaceuticals that are suitable for oral administration in a capsule, and therefore for the present invention.

However, for each individual case, the assistant specialist must determine the prescribed dose. In an individual case, the assistant specialist may choose to use an activity / dose different from that mentioned in the table above. This will be known to the person skilled in the art, for example, as described for the 131I at the following link: http://reference.medscape.com/drug/hicon-sodium-iodide-i-131-999924.

In an embodiment of the method of the invention, said radioactive isotope is radioactive iodine or 99mTc.

In an embodiment of the method of the invention, said radioactive iodine is selected from the group comprising 123I, 1311 and 124I. Non-limiting examples of typical 123I, 131I, and 124I doses are 3.7 MBq, 1,000 MBq, and 74 MBq, respectively.

In an embodiment of the method of the invention, said radioactivity solution is a sodium iodide solution. In an embodiment of the method of the invention, said radioactivity solution is a 99mTc pertechnetate solution

In an embodiment of the method of the invention, said method includes the additional steps, carried out between steps (c) and (d), of:

(c-i) placing the preliminary needle positioner (6), as defined herein, on the capsule holder (2);

(c-ii) introducing a second needle (7b) in the upper section (6f) of the hole (6d) in the upper end (6b) of said preliminary needle positioner (6), in which said second needle (7b) it has a smaller gauge compared to said first needle (7a);

(c-iii) optionally securing said second needle (7b) in place in said needle positioner; (c-iv) drilling with said second needle (7b) a hole in the upper part of the inner cover (3c); Y,

(c-v) remove the preliminary needle positioner (6).

In an embodiment of the method of the invention, said securing step (c-iii) is achieved through securing means (6g) supported within said preliminary needle positioner (6).

In an embodiment of the method of the invention, said securing means (6g) comprise a screw or a spring.

In one embodiment, the method of the invention is automated. The system of the invention comprises components of regular shape and size and the method is easily definable in time and space. As such, one skilled in the art would have no difficulty automating the system and method of the present invention. The automation of the method of the present invention would be convenient in a radiopharmacy filling in the area of up to 10 oral capsules per day.

This description uses examples to disclose the invention, including the best mode, and also to allow any person skilled in the art to practice said invention, including making and using any device or system and performing any incorporated method. In order to more clearly and concisely describe and designate the substantive subject matter of the claimed invention, definitions are provided herein for the specific terms used throughout the present specification and claims. Any exemplification of the specific terms in this specification should be considered as a non-limiting example. The patentable scope of the invention is defined by the claims and may include other examples that occur to those skilled in the art. Such different examples are intended to be within the scope of the claims, if they have structural elements that do not differ from the literal expression of the claims, or if they include equivalent structural elements with non-substantial differences from the literal expressions of the claims.

Examples

Example 1: evaluation of the capsule filling shield

Introduction

A study was conducted to compare the known manual method with the method using an exemplary system of the invention. 10 capsules were filled with a Tc-99m pertechnetate solution (obtained from a Drytec® generator) using the manual technique and 10 capsules were filled using an exemplary method of the invention. The time required for the actual filling process of the capsule was recorded. After the capsules were full, the activity of each capsule was measured on a dose calibrator (Veenstra).

Results

The procedure with the method of the invention was the fastest actual filling process. The results are summarized in the table that follows. The procedure with the method of the invention proved to be twice as fast as manual filling.

Capsule uniformity was determined by measuring activity (patient dose) per capsule. The results are plotted graphically in Figure 8 (where the exemplary system of the invention is called "Capsule Fill Shielding") and are summarized in the table below. Using the USP <905> guidelines, it was shown that, for 10 capsules, the manual method did not meet the criteria mentioned in the USP for 10 units. The method of the invention, in contrast to this, did meet these requirements.

conclusion

The method of the invention was shown to make the capsule filling process twice as fast. Operators also reported reduced chances of spill or needle stick injury. Regarding the uniformity of the capsules, the method of the invention was shown to produce capsules that met USP guidelines. The inventive method provided better uniformity of the capsules compared to the known manual method.

Example 2: Assessment of radiation exposure of the capsule filling shield

Introduction:

A calculation was made to show the effect on exposure to peripheral radiation. The calculation was made for three isotopes of iodine, since these isotopes are mainly used for compound capsules in nuclear pharmacies. The three isotopes of iodine chosen were: I-123, I-124 and I-131. In the calculation, the activity of 3.7 MBq was chosen for I-123, 74 MBq for I-124 and 1,000 MBq for I-131. They represent normal patient doses. Results:

Exposure to hand radiation was calculated for the manual method and the exemplary method of the invention. The results are mentioned in the tables that follow and are plotted graphically in Figure 9 (the invention in Figure 9 is called "CFS", which stands for Capsule Fill Shielding).

conclusion

Exposure to radiation from the hands was calculated for two capsule filling methods. Faster filling and additional shielding with the method of the present invention contributed to a considerable decrease in radiation exposure to the hands. For I-123, the radiation exposure was reduced to almost zero. For I-131, the radiation exposure was reduced by a factor of 394. For I-124, the radiation exposure was reduced by a factor of 17.5. Therefore, the present invention demonstrates that it reduces the radiation load on the hands.

Claims (18)

1. A system (1) comprising: (i) a capsule holder (2) having a lower end (2a) and an upper end (2b), wherein said capsule holder comprises a solid base (2c) located at said lower end (2a), a solid body (2d ) extending upwards from said solid base (2c) and a well (2e) extending downwards inside said solid body (2d), in which said well (2e) ends at the upper end (2b) of said capsule holder (2) and ends before said solid base (2c) and is configured to receive a lower half (3a) of a capsule (3), in which said capsule holder (2) is formed from a shielding material radiation shielding, wherein preferably the radiation shielding material comprises lead, steel or tungsten; (ii) an armored needle positioner (4) having a lower end (4a) and an upper end (4b), wherein said armored needle positioner (4) comprises a solid body (4c) defining a hole ( 4d) extending substantially linearly and centrally therethrough, said hole (4d) comprising a lower section (4e) leading to said lower end (4a), and an upper section (4f) opening to said end upper (4b) and configured to receive an upper half (3b) of a capsule (3), in which said shielded needle positioner (4) is formed from a radiation shielding material, characterized in that said hole it is configured to fit on and contain the solid body of said capsule holder. 2. The system (1) as defined in claim 1, wherein said armored needle positioner (4) further comprises a cap (4g) configured to fit over the upper end (4b) thereof, wherein said The cover comprises a hole (4h) through it, which has a width similar to the upper section (4f) of the hole (4d) of the armored needle positioner (4), in which said cover (4g) is formed at from a radiation shielding material. 3. The system (1) as defined in either claim 1 or claim 2, further comprising: (iii) a preliminary needle positioner (6) having a lower end (6a) and an upper end (6b ), wherein said preliminary needle positioner (6) comprises a body (6c) defining a hole (6d) extending substantially linearly and centrally therethrough, said hole (6d) comprising a lower section ( 6e) leading to said lower end (6a) and configured to fit on and contain the solid body (2d) of said capsule holder (2), and an upper section (6f) leading to said upper end (6b) ) and configured to contain an upper half (3b) of a capsule (3), wherein said shielded needle positioner (6) is formed from a rigid material, wherein preferably said rigid material comprises a rigid plastic, preferably plexiglass. 4. The system (1) as defined in any one of claims 1-3, wherein each of the components is substantially cylindrical. The system (1) as defined in either claim 3 or claim 4, wherein said body (6c) of said preliminary needle positioner (6) is solid or a frame. 6. The system (1) as defined in any one of claims 3-5, further comprising securing means (6g) configured to support a needle within the hole (6d) of said preliminary needle positioner (6), wherein said securing means (6g) preferably comprise a spring or a screw. 7. A method for filling a radioactivity capsule (3), wherein said capsule comprises an inner shell (3c) and an outer shell (3d), wherein said outer shell (3d) comprises a body of smaller diameter ( 3e) and a cover with a larger diameter (3f) and in which said method comprises the following steps: (a) providing the system as defined in claim 1; (b) placing said body of smaller diameter (3e) inside the well (2e) of the capsule holder (2); (c) placing said inner cover (3c) inside said smaller diameter body (3e); (d) place the armored needle positioner (4) on the capsule holder (2) containing the smallest diameter body (3e) and the inner cover (3c) so that the solid body (2d) of the capsule holder (2) is contained within the lower section (4e) of the hole (4d) of the armored needle positioner (4) and an upper half of the inner cover (3c) is contained within the upper section (4f) of the hole (4d) of the positioner armored needle (4); (e) introducing a first needle (7a), attached to a shielded syringe (7) containing a radioactivity solution in the upper section (4f) of the hole (4d), in the upper end (4b) of said needle positioner armored (4); (f) injecting the radioactivity solution into the inner cover (3c); (g) remove the armored needle positioner (4); (h) fixing said larger diameter cover (3f) to said smaller diameter body (3e) so that said inner cover (3c) is safely contained within said outer cover, wherein steps (a) - (h) are preferably carried out sequentially. 8. The method as defined in claim 7, wherein said capsule (3) is suitable for oral administration and is preferably made from a material comprising gelatin or polymer formulated from cellulose, preferably hard gelatin. The method as defined in any one of claim 7 or claim 8, wherein said inner shell (3c) contains an absorbent buffer solution, wherein said absorbent buffer solution preferably comprises a hydroscopic crystalline powder, preferably phosphate of Dibasic Anhydrous Sodium USP. The method as defined in any one of claims 7-9, wherein said inner shell (3c) contains a stabilizer, wherein said stabilizer is preferably disodium edetate dihydrate. 11. The method as defined in any one of claims 7-10, wherein said inner shell (3c) contains a reducing agent, wherein said reducing agent is preferably sodium thiosulfate pentahydrate. 12. The method as defined in any one of claims 7-11, wherein, at the end of said method, the pH of the content of said inner shell (3c) is in the range of 7.5 to 9.0 . 13. The method as defined in any one of claims 7-12, wherein said radioactivity solution comprises a radioactive isotope suitable for use as an orally administered radiopharmaceutical, wherein said radioactive isotope is radioactive iodine selected from 123I , 131I and 124I, or 99mTc. 14. The method as defined in any one of claims 7-13, wherein said radioactivity solution is a sodium iodide solution. 15. The method as defined in any one of claims 7-13, wherein said radioactivity solution is a 99mTc pertechnetate solution. 16. The method as defined in any one of claims 7-15, wherein said method includes the additional steps, carried out between steps (c) and (d), of: (c-i) placing the preliminary needle positioner (6), as defined in claim 4, on the capsule holder (2); (c-ii) introducing a second needle (7b) in the upper section (6f) of the hole (6d) in the upper end (6b) of said preliminary needle positioner (6), in which said second needle (7b) it has a smaller gauge compared to said first needle (7a); (c-iii) optionally securing said second needle (7b) in place in said needle positioner; (c-iv) drilling a hole in the upper part of the inner cover (3c) with said second needle (7b); and, (c-v) remove the preliminary needle positioner (6). 17. The method as defined in claim 16, wherein said securing step (c-iii) is achieved through securing means (6g), preferably a screw or a spring, supported within said needle positioner preliminary (6). 18. The method as defined in any one of claims 7-17, which is automated.